Spin hyperpolarization methods have enabled essential developments in preclinical and clinical MRI applications to overcome the intrinsic low level of sensitivity of nuclear magnetic resonance. imaging is considered as the realm in which the spatial distribution of different cellular and biochemical guidelines occurring in the molecular level is definitely displayed using different detection modalities. E7820 These include magnetic resonance imaging (MRI), fluorescence imaging (FI), ultrasound (US), and positron-emission tomography (PET). They all have shown their usefulness as a valuable (pre-)medical molecular imaging tool in different contexts. Various elements need to be regarded as for each individual application (large quantity of the prospective of interest, synthesis of the reporter, desired spatial and temporal image resolution, radiation burden, translational elements, etc.), and each modality offers its own pros and cons. In this context, MRI serves as one of the regularly used medical imaging techniques due to its unlimited penetration depth and its capability to generate high-contrast images of different smooth tissues with adequate spatial resolution. Although MRI offers important capabilities that are vital for molecular imaging, it suffers considerably from a lack of level of sensitivity. Any recognized macroscopic magnetization requires a large spin density and thus typically also a relative high concentration of contrast providers  that take action on the recognized bulk magnetization. A plethora of MRI contrast agents have been reported throughout many preclinical studies to address the aforementioned sensitivity issue and to explore the options of responsive agents . In spite of tremendous rise in generation of new MRI contrast agents, mostly gadolinium (Gd3+)-based coordination complexes have found a major use in clinics, followed by superparamagnetic iron oxide nanoparticles (SPIONs ) in many preclinical studies. The MRI-active center like Gd3+ nuclei and Fe2+/Fe3+ spin states in SPIONs are capable of relaxing water protons that are available in their immediate vicinity, thus causing accelerated recovery of longitudinal magnetization (positive contrast, conditions is ongoing. Hyperpolarized agents are currently explored in many studies as they E7820 address the sensitivity issue and do not require (super-) paramagnetic substances acting on the bulk water magnetization. They allow direct detection of dilute spin pools in compounds other than water. Xenon biosensors are one class of hyperpolarized (hp) reporters. Despite their different mechanism of action, their specific design is worth being discussed in the context of nanoparticle agents known from 1H MRI. Unlike Gd-based agents, SPIONs and other related nanoparticles come with a large set of parameters to tune their behavior and relaxivity performance. Owing to their tunable size, SPIONs might easily extravasate into the leaky interstitial space and vasculature of different tumors, thereby leading E7820 to a nonspecific accumulation in tumors via an enhanced permeation and retention (EPR) effect. The EPR effect is fostered by macrophages and the reticuloendothelial systems (e.g., liver and spleen). Beyond such nonspecific accumulation, numerous targeted iron oxide nanoparticle-based MRI contrast agents have also been reported for preclinical imaging F2rl3 of different cancer cells and tumors. The challenge with SPIONs and their ultrasmall version (USPIONs, 1C20?nm) is still that they cause a passive signal cancellation and cannot be activated for switchable contrast through the MRI pulse sequence. The latter aspect is a feature E7820 that came with the advent of CEST agents, translation of nanoparticle-based Xe biosensors will be reviewed, followed by suggestions to improve E7820 their performance for future applications. 2. General Considerations for Hyperpolarized 129Xe NMR 2.1. Production of Hyperpolarized Xe The noble gas 129Xe is typically hyperpolarized using spin exchange optical pumping (SEOP) [20C22]. In this process, the valence electron of vaporized Rb (emitted from a heated Rb droplet, melting point: 39.3C) serves as a polarization precursor. The alkali metal is optically pumped on its D1 transition by a strong infrared laser (795?nm; 102C103?W cw power) that illuminates a.